Gliederung

Introduction: Adjuvant high dose Interferon-alfa 2b prolongs overall survival in patients with malignant melanoma in stage IIc and III, as documented in two of three randomized, multicenter studies performed by J. Kirkwood. Unfortunately, this combined, intravenously and subcutaneously administered cytokine treatment induces grade III/IV toxicities in 50 to 70 % of the patients. Since for multiple reasons the i.v. phase of the treatment seems to be the most relevant part of this therapy, we performed a feasibility study (phase II) by giving patients three four week i.v. cycles (5x20 Mio/m2 I.E.IFN-alfa-2b per week), each i.v. cycle separated from the next by 4 months non treatment.

Results: 46 patients with large primary tumor (n=4) or regional lymph node metastasis (n=42) were treated according to the above mentioned regimen. At present 41 patients are evaluable. Only 8 patients (19,5%) experienced grade III/IV toxicity. No therapy related death was observed. In 8 patients (19,5%)short treatment interruptions (<4 days)were necessary. 7 patients (17%) required a 50% dose reduction. Interestingly, Mx proteins specifically induced by type I IFNs were monitored in circulating leukocytes while patients on treatment. The protein level increased significantly in each i.v.cycle. After one year of follow up only 9 of 33 patients showed a recurrence of their malignant melanoma.

Conclusions: The data of our phase II study clearly demonstrate the feasibility of the regimen tested. Therapy related toxicities seem to be less intense and less frequent than side effects reported by Kirkwood in his three large multicenter studies. At present only 25,3 % of the patients experienced a relapse of their disease. A large multicenter trial comparing our regimen with the classical Kirkwood treatment has been initiated by ADO and AIO.